The long-term objective of this project is to understand in detail the molecular mechanisms of Rev. Toward this end, the investigator proposes to define the features of the viral RNA element, designated the Rev-responsive element (RRE), required for Rev recognition. Protein-fusion experiments will be used to assess whether the sole function of the viral RRE is to provide a Rev binding site. A major emphasis of the project will be to determine the molecular mechanism by which Rev increases the cytoplasmic accumulation of RRE-containing viral RNAs. In particular, the investigator proposes to identify cellular polypeptide(s) with which the Rev effector domain interacts. The applicant also will attempt to establish in vitro systems to study Rev function and to address the possibility that Rev directly regulates pre-mRNA splicing. Mutational analysis indicates that some Rev mutants have a dominant-negative phenotype. These dominant-negative Rev mutants have the potential to block viral replication. The applicant intends to explore the basis of the dominant-negative phenotype and to test their ability to function as anti-viral agents.